Primary cilia function as critical sensory organelles that mediate multiple signaling pathways, including the Hedgehog (Hh) pathway, which is essential for organ patterning and morphogenesis. Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice. Cilk1, a highly conserved serine/threonine-protein kinase localized within primary cilia, plays a critical role in ciliary transport. Loss of Cilk1 results in severe ciliopathy phenotypes, including polydactyly, edema, and cleft palate. However, the role of Cilk1 in tooth development remains unexplored. In this study, we investigated the role of Cilk1 in tooth development. Cilk1 was found to be expressed in both the epithelial and mesenchymal compartments of developing molars. Cilk1 deficiency resulted in altered ciliary dynamics, characterized by reduced frequency and increased length, accompanied by downregulation of Hh target genes, such as Ptch1 and Sostdc1, leading to the formation of diastemal supernumerary teeth. Furthermore, in Cilk1^-/-;PCS1-MRCS1^△/△ mice, which exhibit a compounded suppression of Hh signaling, we uncovered a novel phenomenon: diastemal supernumerary teeth can be larger than first molars. Based on these findings, we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning: initially inducing diastemal supernumerary teeth, then enlarging them, and ultimately leading to molar fusion. This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.
Animals ; Hedgehog Proteins/physiology* ; Mice ; Signal Transduction/physiology* ; Tooth, Supernumerary ; Molar ; Cilia/physiology* ; Odontogenesis/physiology* ; Patched-1 Receptor ; Protein Serine-Threonine Kinases/physiology* ; Mice, Knockout ; Adaptor Proteins, Signal Transducing

Background: While polystyrene microplastics (PS-MPs) are emerging as potentially significant health threats, linked to cancer and reproductive dysfunction, their precise effects on human health remain largely unknown. We aimed to investigate the underlying mechanisms promoting microplastic-induced damage in the reproductive system. Methods: Thirty C57BL/6 male mice were randomly allocated into six equal-sized groups.Mice were exposed to fluorescent PS-MPs (5 µm, < 18%, green) at a dose of 1 and 3 mg/dL via oral gavage for 28 and 56 days, respectively (control, 0 mg/dL). The presence of antibodies and inflammatory and oxidative stress markers were evaluated using western blotting. Sperm analysis was also performed. Mouse testis Sertoli TM4 cells were divided into two groups:control (medium only) and PS-MPs (medium containing, 1,000 μg/mL) groups and cultured in vitro for 1, 24, 48, or 72 hours. The cells were cultured in a Ham’s F12: Dulbecco's Modified Eagle Medium medium with 0.25% fetal bovine serum at 37°C with humidified atmosphere of 5% carbon dioxide in the air. Protein analyses for interleukin (IL)-6, IL-10, NADPH-oxidase (NOX)-2, NOX-4, hypoxia-inducible transcription factor (HIF)-2α, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β were performed using western blotting. Results: The testes were evaluated after 28 and 56 days of exposure. Varying sizes of PS-MPs were detected in the testes (ranging from 5.870 to 7.768 µm). Significant differences in sperm concentration, motility, and the proportion of normal sperm were observed between the two groups. An increase in TGF-β, HIF-2α, and NOX-4 levels was observed using western blot analysis. However, no dose-dependent correlations were observed between the two groups.In vitro evaluation of the PS-MPs group displayed PS-MP penetration of the lumen of Sertoli cells after 1 hour. Further PS-MP aggregation within Sertoli cells was observed at 24, 48, and 72 hours. A significant increase in inflammatory protein expressions (IL-10, TGF-β, MCP-1, IL-6, TNF-α, and HIF-2α) was observed through western blotting, although oxidative agents did not show a significant increase. Conclusion PS-MPs induced reproductive dysfunction in male mice provide new insights into PS-MPs-associated toxicity in mammals.

Kaposi’s varicelliform eruption (KVE) is a rare viral infection primarily caused by herpes simplex virus (HSV). This condition frequently presents concomitantly with underlying chronic skin disorders, particularly atopic dermatitis (AD). This report describes a rare case of sepsis resulting from KVE in a patient with AD. A 30-year-old male patient with a history of AD presented with painful skin lesions characterized by papulovesicular eruptions, crusts, erythema, and erosions, initially localized to the neck and spreading throughout his body, accompanied by a high fever. Laboratory findings confirmed HSV infection and sepsis. Thus, a diagnosis of KVE compounded by sepsis was established. Systemic acyclovir and antibiotics led to complete recovery within 3 weeks, with resolution of fever and skin manifestations, and general health improvement. Timely recognition and management of KVE are crucial for prevention of adverse outcomes. Both physicians and patients with AD should be made aware of the predisposing factors and risks associated with KVE.

Congenital smooth muscle hamartoma is a benign proliferation of smooth muscles within the dermis. The classic form presents as well-defined, skin-colored, or hyperpigmented plaques associated with hypertrichosis. However, there have been reports of atypical forms, including a follicular spotted appearance, linear atrophic plaques, and morphea-like forms. In such cases, distinguishing congenital smooth muscle hamartomas from other cutaneous diseases can be challenging. Herein, we report on a 16-month-old boy who presented with a hypopigmented patch and hypertrichosis on his back since birth. Histopathological examination revealed mild acanthosis and well-defined smooth muscle bundles haphazardly oriented in the dermis. These bundles stained positively with Masson’s trichrome stain. Based on these findings, a definitive diagnosis of congenital smooth muscle hamartoma was established. In conclusion, an exceptionally rare case of congenital smooth muscle hamartoma with a hypopigmented appearance is reported.

Background: Female-pattern hair loss (FPHL) is characterized by diffuse hair thinning in the mid-frontal scalp and increased hair shedding. Although the use of low-dose oral minoxidil (LDOM) is increasing significantly in Korea, data on its use are limited. Objective: To determine the efficacy and safety of LDOM in Korean patients with FPHL. Methods: This retrospective, single-center study was conducted at Pusan National University Hospital. The study included female patients with pattern hair loss who received treatment with LDOM at 1.25 mg/d for a minimum of 6 months in combination with other treatments. Patients were eligible for LDOM addition if their previous treatments showed a limited response and the previous treatment regimen remained unchanged throughout the evaluation period. Clinical response to treatment was evaluated using the Sinclair hair loss severity scale. Results: The study included 44 females with FPHL. Before treatment, the mean Sinclair scale score was 2.77, which decreased to 2.27 after treatment. By the 3rd month, one patient (2.3%) experienced worsening, while seven patients (15.9%) showed slight improvement. By the 6th month, the treatment response was as follows: stabilization in 30 patients (68.2%), slight improvement in 13 patients (29.5%), and substantial improvement in one patient (2.3%). Adverse effects, predominantly hypertrichosis, were observed in nine patients. All adverse effects improved upon discontinuation of LDOM and no life-threatening adverse effects were observed during the study. Conclusion This study provides evidence that LDOM can be an effective therapeutic option with a good safety profile for FPHL.

Dupilumab, a human monoclonal antibody targeting the interleukin-4 receptor α, has exhibited rapid and remarkable therapeutic efficacy in numerous clinical trials focusing on moderate-to-severe atopic dermatitis and prurigo nodularis. Nonetheless, instances of mycosis fungoides have been reported in patients undergoing dupilumab treatment for atopic dermatitis. We present two cases: a 36-year-old woman and a 64-year-old man who presented to our dermatology clinic with erythematous papules and plaques. Following skin biopsy, both patients were diagnosed with chronic eczematous dermatitis with prurigo. Erythematous plaques notably increased after 9 months and 1 month of dupilumab treatment, respectively. Subsequent biopsies confirmed histopathological markers consistent with mycosis fungoides. The first patient underwent chemotherapy for lymph node metastasis, while the second received oral acitretin, narrow-band ultraviolet B, and topical corticosteroids.

The survival rate of children admitted in the neonatal intensive care unit (NICU) after birth is on the increase; hence, proper evaluation and care of their neurodevelopment has become an important issue. Neurodevelopmental assessments of individual domains regarding motor, language, cognition, and sensory perception are crucial in planning prompt interventions for neonates requiring immediate support and rehabilitation treatment. These assessments are essential for identifying areas of weakness and designing targeted interventions to improve future functional outcomes and the quality of lives for both the infants and their families. However, initial stratification of risk to select those who are in danger of neurodevelopmental disorders is also important in terms of cost-effectiveness. Efficient and robust functional evaluations to recognize early signs of developmental disorders will help NICU graduates receive interventions and enhance functional capabilities if needed. Several age-dependent, domain-specific neurodevelopmental assessment tools are available; therefore, this review summarizes the characteristics of these tools and aims to develop multidimensional, standardized, and regular follow-up plans for NICU graduates in Korea.

Background: and PurposePeripheral neuropathies (PNs) are a common but poorly understood complication of chronic obstructive pulmonary disease (COPD). To clarify the initial trigger of a PN in COPD, we investigated the excitability of peripheral nerves in patients with COPD. Methods: The automated nerve excitability test (NET) using the threshold-tracking paradigm was applied to 20 COPD patients. The recording protocol calculated the strength–duration time constant, threshold electrotonus (TE), current–threshold relationship, and recovery cycle (RC). Each NET parameter was compared with two control groups: normal controls group (NC group) and smokers without COPD group (smoker group). Results: In the motor NETs, the change in the threshold in the mid-depolarizing phase of TE (40–60 ms) was smaller in the COPD group (50.7%±1.2%, mean±SEM; n=20) than in the NC group (54.5%±0.7%, n=25; p<0.01), as was the prominence of superexcitability in the RC (-22.6%±1.5% and -26.4%±1.1%, respectively; p=0.04). There were no significant differences in the sensory NETs. Comparisons between the COPD and smoker groups (n=25) also showed no differences in either the motor or sensory NETs. Conclusions The pattern of excitability in COPD revealed a membrane depolarization attributable to Na+–K+–ATPase failure in the axolemma of distal motor nerves. This finding suggests that chronic hypoxemia and adaptative process can alter axonal excitability and trigger a resultant neuropathic process that is antecedent to PN in COPD.

Background: Data illustrating the impact of atopic dermatitis (AD) on lives of adults with AD in South Korea are limited. Objective: To assess the AD disease severity and its impact on quality of life (QoL) in patients with AD from South Korea. Methods: Patients with AD utilizing the specialist dermatology services of major hospitals in South Korea were assessed for disease severity using Eczema Area and Severity Index (EASI) score, for QoL using Dermatology Life Quality Index (DLQI) (for QoL), and for comorbidities and treatment experience via retrospective review of 12-month medical records. Clinical and sociodemographic characteristics were also measured. Results: Of the 1,163 patients, 695 (59.8%) were men (mean age [years]±standard deviation: 31.6±12.1). Overall, 52.9% (n=615) patients had moderate-to-severe disease (EASI>7).The QoL of 72.3% (n=840) patients was affected moderately-to-severely (DLQI score: 6~30).Systemic immunosuppressants were used ≥1 over past 12 months in 51.9% (n=603) patients, and the most commonly used were cyclosporines (45.7%, n=531) and systemic corticosteroids (40.5%, n=471). Approximately, 10.8% (n=126) patients consulted or received treatment for AD-related eye problem. Of these, 40% (n=50) patients reported poor, very poor, or completely blind status; approximately, 16.7% patients (n=192) reported having depression or anxiety; and 35.5% (n=410) reported suicidal ideation or suicidal attempt. Conclusion A large proportion of patients had moderate-to-severe AD, a compromised QoL, and ocular or mental health comorbidities, indicating a high disease burden despite systemic treatment. These findings highlight the importance of a holistic approach for the evaluation and treatment of patients with AD.